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Structure of the BRK domain of the SWI/SNF chromatin remodeling complex subunit BRG1 reveals a potential role in protein-protein interactions.
Protein Science ( IF 4.5 ) Pub Date : 2020-01-13 , DOI: 10.1002/pro.3820
Mark D Allen 1 , Mark Bycroft 1 , Giovanna Zinzalla 2
Affiliation  

BRG1/SMARCA4 and its paralog BRM/SMARCA2 are the ATPase subunits of human SWI/SNF chromatin remodeling complexes. These multisubunit assemblies can act as either tumor suppressors or drivers of cancer, and inhibiting both BRG1 and BRM, is emerging as an effective therapeutic strategy in diverse cancers. BRG1 and BRM contain a BRK domain. The function of this domain is unknown, but it is often found in proteins involved in transcription and developmental signaling in higher eukaryotes, in particular in proteins that remodel chromatin. We report the NMR structure of the BRG1 BRK domain. It shows similarity to the glycine-tyrosine-phenylalanine (GYF) domain, an established protein-protein interaction module. Computational peptide-binding-site analysis of the BRK domain identifies a binding site that coincides with a highly conserved groove on the surface of the protein. This sets the scene for experiments to elucidate the role of this domain, and evaluate the potential of targeting it for cancer therapy.

中文翻译:

SWI / SNF染色质重塑复杂亚基BRG1的BRK结构域揭示了蛋白质相互作用中的潜在作用。

BRG1 / SMARCA4及其类似物BRM / SMARCA2是人SWI / SNF染色质重塑复合物的ATPase亚基。这些多亚基装配体既可以充当癌症的肿瘤抑制因子,也可以充当癌症的驱动因子,并且抑制BRG1和BRM都已成为各种癌症中一种有效的治疗策略。BRG1和BRM包含一个BRK域。该结构域的功能是未知的,但通常在涉及高等真核生物的转录和发育信号的蛋白质中,特别是在重塑染色质的蛋白质中发现。我们报告了BRG1 BRK域的NMR结构。它与甘氨酸-酪氨酸-苯丙氨酸(GYF)域(已建立的蛋白质-蛋白质相互作用模块)相似。BRK结构域的计算肽结合位点分析确定了与蛋白表面上高度保守的凹槽重合的结合位点。这为进行实验阐明该域的作用,并评估靶向该域用于癌症治疗的潜力奠定了基础。
更新日期:2020-01-13
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